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標題: | 半乳糖凝集素-3在腸病毒71型感染中所扮演之角色 Role of Galectin-3 in Enterovirus 71 Infection |
作者: | Wen-Chan Huang 黃文嬋 |
指導教授: | 劉扶東 |
共同指導教授: | 張鑾英 |
關鍵字: | 半乳糖凝集素-3,腸病毒71型,感染,單核?酸多型性, Enterovirus infection,EV71,galectin-3,hyperglycemia,single nucleotide polymorphism,viral load, |
出版年 : | 2017 |
學位: | 博士 |
摘要: | 半乳糖凝集素-3(Galectin-3)是一種嵌合蛋白,具有與β-半乳糖結合的能力,Galectin-3可藉由與細胞內其他蛋白的結合,或是調控細胞內的訊息傳導路徑,進而影響細胞內多種生理功能,如細胞凋亡、免疫細胞的噬菌能力、肥大細胞的成熟過程,以及T細胞的活化。然而,目前的研究仍未釐清Galectin-3在腸病毒71型(EV71)感染所扮演的角色。我們的研究發現,當橫紋肌肉瘤細胞(Rhabdomyosarcoma cell, RD cells)缺乏galectin-3時,EV71在細胞內與釋出的病毒量都有顯著的減少;此外,當RD cells表現Galectin-3的單核苷酸多型性rs4644時,EV71的病毒量也會較wild-type RD cells少。於臨床方面,我們發現感染EV71 且具有高血糖的幼童中,帶有rs4644 AA基因型的幼童,其住院期間的最高血糖值(2.2 ± 0.06 log10 mg/dL)較其他兩種基因型CC(2.4 ± 0.17 log10 mg/dL, P = 0.03)與CA(2.4 ± 0.15 log10 mg/dL, P = 0.02)基因型的幼童低,由於高血糖已知為腸病毒重症之危險因子,我們的研究發現Galectin-3不僅影響腸病毒感染,也與感染時病人之高血糖值有關,期待未來更多相關的研究能更深入探討Galectin-3如何影響 EV71感染,以及高血糖的相關機制。 Galectin-3, a chimeric type β-galactoside-binding protein, is known to modulate viral infection; however, its role in enterovirus 71 (EV71) infection has not been investigated. We generated galectin-3 null rhabdomyosarcoma (RD) cells and evaluated whether EV71 infection would be affected. Deletion of galectin-3 resulted in a significant reduction of the released and intracellular EV71 viral loads, as well as cell death rates, 24 h after infection. Yet, it did not affect cell proliferation. In addition, RD cells expressing a nonsynonymous genetic variant of galectin-3, rs4644 (LGALS3 +191C/A, P64H), produced lower virus titers than those with wild-type galectin-3 (C allele). To clarify whether the in vitro viral load reduction associated with rs4644 correlates with clinical severity, we enrolled children with laboratory-confirmed EV71 infection. Since hyperglycemia is an indicator of severe EV71 infection in children, 152 of 401 enrolled children had glucose examinations at admission, and 59 subjects had serum glucose levels ≥ 150 mg/dL. In comparison to the rs4644 AA genotype (2.2 ± 0.06 log10 mg/dL), serum glucose levels during EV71 infection were higher in patients with CC (2.4 ± 0.17 log10 mg/dL, P = 0.03) and CA (2.4 ± 0.15 log10 mg/dL, P = 0.02) genotypes, respectively. These findings suggest that the rs4644 AA genotype of galectin-3 might exert a protective effect. In summary, galectin-3 affects EV71 replication in our cellular model and its variant, rs4644, is associated with hyperglycemia in the clinical setting. The underlying mechanism and its potential therapeutic application warrant further investigation. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59862 |
DOI: | 10.6342/NTU201700369 |
全文授權: | 有償授權 |
顯示於系所單位: | 轉譯醫學博士學位學程 |
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